We should not underestimate the role of biofilms in persistent (chronic) bronchitis
Authors: Mark Lloyd Everard
Journal: The Lancet Microbe (2022)

The study by Robyn L Marsh and colleagues1Marsh RL Binks MJ Smith-Vaughan HC et al.Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study.Lancet Microbe. 2022; 3: e215-e223Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar suggests that lower airway biofilms have an important role in persistent (chronic) bacterial bronchitis in children. However, the authors' conclusion—that lower airway biofilms are not ubiquitous—depends on the assumption that a bronchoalveolar lavage will identify biofilms if they are present; however, there are many reasons why false negative results might be obtained in this setting.First, in many patients with chronic bacterial bronchitis, the disease involves only a few lobes or segments of a lobe. Indeed, the more lobes that are lavaged in a patient with persistent bacterial bronchitis, the more likely one is to obtain a positive culture.2Narang R Bakewell K Peach J et al.Bacterial distribution in the lungs of children with protracted bacterial bronchitis.PLoS One. 2014; 9e108523Crossref Scopus (30) Google Scholar Second, the challenges posed by the non-homogeneous distribution of bacteria in sputum and bronchoalveolar lavage samples has been recognised for at least 70 years. In a 2020 study involving young patients with persistent bacterial bronchitis from whom aliquots of the same bronchoalveolar lavage sample were sent to two accredited laboratories, the two laboratories generated very different results for the majority of samples.3Craven V Hausdorff WP Everard ML High levels of inherent variability in microbiological assessment of bronchoalveolar lavage samples from children with persistent bacterial bronchitis and healthy controls.Pediatr Pulmonol. 2020; 55: 3209-3214Crossref PubMed Scopus (3) Google Scholar This finding was replicated when aliquots from the same sample were analysed by the same laboratory (Everard M L, unpublished). Third, biofilms are—with the exception of those formed by Pseudomonas—believed to be attached to the endobronchial surface, a feature that limits disruption and dispersion by physical forces. This characteristic is likely, in many cases, to prevent the recovery of biofilm communities even if they are present in the lobe. Fourth, several factors, such as antibiotic use and intercurrent viral infections, impact the metabolism and behaviour of bacteria in biofilms and might influence the likelihood of disrupting biofilms. Finally, the authors considered biofilms to have originated in the upper airways when there were more than ten squamous cells per 1000 nucleated cells, ignoring the fact that squamous metaplasia within bronchi has long been known to be a feature of bronchiectasis and has been described in children without bronchiectasis;4Mithal A Emery JL Squamous metaplasia of the tracheal epithelium in children.Thorax. 1976; 31: 167-171Crossref PubMed Scopus (14) Google Scholar hence, their assumption might have lowered the number of true positive cases.Given the impact of vaccines on the prevalence of bacteria that are particularly adept at forming biofilms and the increasing antibiotic resistance of these bacteria,5Heinz E The return of Pfeiffer's bacillus: rising incidence of ampicillin resistance in Haemophilus influenzae.Microb Genom. 2018; 4e000214PubMed Google Scholar it is crucial that non-antibiotic treatment approaches, which include biofilm disruptors, are not ignored due to the misinterpretation of data in this study. The study by Robyn L Marsh and colleagues1Marsh RL Binks MJ Smith-Vaughan HC et al.Prevalence and subtyping of biofilms present in bronchoalveolar lavage from children with protracted bacterial bronchitis or non-cystic fibrosis bronchiectasis: a cross-sectional study.Lancet Microbe. 2022; 3: e215-e223Summary Full Text Full Text PDF PubMed Scopus (2) Google Scholar suggests that lower airway biofilms have an important role in persistent (chronic) bacterial bronchitis in children. However, the authors' conclusion—that lower airway biofilms are not ubiquitous—depends on the assumption that a bronchoalveolar lavage will identify biofilms if they are present; however, there are many reasons why false negative results might be obtained in this setting. First, in many patients with chronic bacterial bronchitis, the disease involves only a few lobes or segments of a lobe. Indeed, the more lobes that are lavaged in a patient with persistent bacterial bronchitis, the more likely one is to obtain a positive culture.2Narang R Bakewell K Peach J et al.Bacterial distribution in the lungs of children with protracted bacterial bronchitis.PLoS One. 2014; 9e108523Crossref Scopus (30) Google Scholar Second, the challenges posed by the non-homogeneous distribution of bacteria in sputum and bronchoalveolar lavage samples has been recognised for at least 70 years. In a 2020 study involving young patients with persistent bacterial bronchitis from whom aliquots of the same bronchoalveolar lavage sample were sent to two accredited laboratories, the two laboratories generated very different results for the majority of samples.3Craven V Hausdorff WP Everard ML High levels of inherent variability in microbiological assessment of bronchoalveolar lavage samples from children with persistent bacterial bronchitis and healthy controls.Pediatr Pulmonol. 2020; 55: 3209-3214Crossref PubMed Scopus (3) Google Scholar This finding was replicated when aliquots from the same sample were analysed by the same laboratory (Everard M L, unpublished). Third, biofilms are—with the exception of those formed by Pseudomonas—believed to be attached to the endobronchial surface, a feature that limits disruption and dispersion by physical forces. This characteristic is likely, in many cases, to prevent the recovery of biofilm communities even if they are present in the lobe. Fourth, several factors, such as antibiotic use and intercurrent viral infections, impact the metabolism and behaviour of bacteria in biofilms and might influence the likelihood of disrupting biofilms. Finally, the authors considered biofilms to have originated in the upper airways when there were more than ten squamous cells per 1000 nucleated cells, ignoring the fact that squamous metaplasia within bronchi has long been known to be a feature of bronchiectasis and has been described in children without bronchiectasis;4Mithal A Emery JL Squamous metaplasia of the tracheal epithelium in children.Thorax. 1976; 31: 167-171Crossref PubMed Scopus (14) Google Scholar hence, their assumption might have lowered the number of true positive cases. Given the impact of vaccines on the prevalence of bacteria that are particularly adept at forming biofilms and the increasing antibiotic resistance of these bacteria,5Heinz E The return of Pfeiffer's bacillus: rising incidence of ampicillin resistance in Haemophilus influenzae.Microb Genom. 2018; 4e000214PubMed Google Scholar it is crucial that non-antibiotic treatment approaches, which include biofilm disruptors, are not ignored due to the misinterpretation of data in this study. I declare no competing interests. We should not underestimate the role of biofilms in persistent (chronic) bronchitis – Authors' replyWe thank Mark Lloyd Everard for his comments and interest in our paper.1 The main point raised relates to the risk of false negative biofilm results and our interpretation therefore minimising the perceived requirement for anti-biofilm treatments. We agree that there is a need to understand whether anti-biofilm treatments improve outcomes in patients with protracted bacterial bronchitis or bronchiectasis; however, data are scarce. Indeed, we are unaware of any guidelines for paediatric protracted bacterial bronchitis and bronchiectasis that recommend anti-biofilm treatments. Full-Text PDF Open Access